Social interaction as an alternative to cocaine

Recovering drug addicts have severe deficits in social interaction, regularly preferring their drug of abuse to interacting with others, including their therapists. Treatment success therefore heavily depends on the addict`s reorientation away from the drug of abuse toward social interaction. Using a behavioral paradigm developed by us, we propose to investigate in C57BL/6N mice if preference vs avoidance of contextual stimuli associated with dyadic social interaction is a predictor of (a) the degree of the subsequent development of a conditioned place preference (CPP) for cocaine, (b) the success of counterconditioning with social interaction, and (c) the risk of a `relapse`, i.e., the degree of reacquisition of cocaine CPP after a final cocaine challenge. We also propose to investigate which neuron types in the medial nucleus accumbens, i.e., D1- and/or D2-dopamine receptor expressing medium spiny neurons (i.e., GABAergic projections neurons) and/or NPY-, parvalbumin- or calretinin- positive GABAergic interneurons and/or cholinergic interneurons are involved in the behavioral changes. Finally, we propose to investigate in which of these neuron types the behavioral changes are paralleled by changes in markers of social preference/avoidance and cocaine exposure, i.e., the density of stubby, thin, and mushroom spines and the expression of RAS-related C3 botulinum substrate 1 (RAC1) and IkB kinase (IKK). In particular, we intend to test the following hypotheses at the quantitative level: (1) Mice that prefer social interaction-associated stimuli, i.e., show CPP for social interaction, should show a differential neuron type activation and/or spine plasticity and/or RAC1- and IKK activation than mice avoiding social interaction-associated contextual stimuli, i.e., show CPA for social interaction. (2) Social avoidance (CPA) and cocaine preference (CPP) should affect these neuron types/markers in a similar way. (3) Counterconditioning with social interaction is expected to reverse the changes in neural activation patterns, dendritic spine morphology and protein markers induced by cocaine preference (CPP) and social avoidance (CPA) should enhance the abovementioned changes. (4) Social interaction counterconditioning should dampen the structural/molecular changes by the subsequent cocaine challenge. (5) Which will prove to be the most sensitive and selective marker? The proposed experiments are of relevance not only for the diagnosis and treamtent of substance use disorders but for those of other psychiatric disorders with impaired social interaction as well, such as depression or autism spectrum disorders.

Recovering drug addicts have severe deficits in social interaction, regularly preferring their drug of abuse to interacting with others, including their therapists. Treatment success therefore heavily depends on the addict`s reorientation away from the drug of abuse toward social interaction. With the help of an animal model developed by us we have studied in mice which neural networks are involved in this reorientation and how one might help the dependent person and her/his social environment with this therapeutically beneficial reorientation. The experiments that were performed with the support of the FWF are of relevance not only for the diagnosis and treatment of substance use disorders but for the diagnosis and treatment of other psychiatric disorders with impaired social interaction as well, such as depression or autism spectrum disorders. In the course of the present FWF projects it became increasingly clear that there are individuals for whom a certain form of social interaction, i.e., power wielding and dominance, has abuse liability. These individuals are addicted to power wielding and show a characteristic behavior which we have described as power abuse disorder. Our current translational research aims at operationalizing this human behavior in animals, preferably mice.